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Diabetologia
Erschienen in: Diabetologia 1/2013

01.01.2013 | Article

Ephedrine activates brown adipose tissue in lean but not obese humans

verfasst von: A. L. Carey, M. F. Formosa, B. Van Every, D. Bertovic, N. Eikelis, G. W. Lambert, V. Kalff, S. J. Duffy, M. H. Cherk, B. A. Kingwell

Erschienen in: Diabetologia | Ausgabe 1/2013

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Abstract

Aims/hypothesis

Brown adipose tissue (BAT) activation increases energy consumption and may help in the treatment of obesity. Cold exposure is the main physiological stimulus for BAT thermogenesis and the sympathetic nervous system, which innervates BAT, is essential in this process. However, cold-induced BAT activation is impaired in obese humans. To explore the therapeutic potential of BAT, it is essential to determine whether pharmacological agents can activate BAT.

Methods

We aimed to determine whether BAT can be activated in lean and obese humans after acute administration of an orally bioavailable sympathomimetic. In a randomised, double-blinded, crossover trial, we administered 2.5 mg/kg of oral ephedrine to nine lean (BMI 22 ± 1 kg/m2) and nine obese (BMI 36 ± 1 kg/m2) young men. On a separate day, a placebo was administered to the same participants. BAT activity was assessed by measuring glucose uptake with [18F]fluorodeoxyglucose and positron emission tomography–computed tomography imaging.

Results

BAT activity was increased by ephedrine compared with placebo in the lean, but unchanged in the obese, participants. The change in BAT activity after ephedrine compared with placebo was negatively correlated with various indices of body fatness.

Conclusions/interpretation

BAT can be activated via acute, oral administration of the sympathomimetic ephedrine in lean, but not in obese humans.
Literatur
1.
Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359PubMedCrossRef
2.
Cypess AM, Lehman S, Williams G et al (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360:1509–1517PubMedCrossRef
3.
Nedergaard J, Bengtsson T, Cannon B (2007) Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 293:E444–E452PubMedCrossRef
4.
Saito M, Okamatsu-Ogura Y, Matsushita M et al (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58:1526–1531PubMedCrossRef
5.
van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM et al (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360:1500–1508PubMedCrossRef
6.
Virtanen KA, Lidell ME, Orava J et al (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360:1518–1525PubMedCrossRef
7.
Zingaretti MC, Crosta F, Vitali A et al (2009) The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J 23:3113–3120PubMedCrossRef
8.
Himms-Hagen J (1979) Obesity may be due to a malfunctioning of brown fat. Can Med Assoc J 121:1361–1364PubMed
9.
Rothwell NJ, Stock MJ (1979) A role for brown adipose tissue in diet-induced thermogenesis. Nature 281:31–35PubMedCrossRef
10.
Bartelt A, Bruns OT, Reimer R et al (2011) Brown adipose tissue activity controls triglyceride clearance. Nat Med 17:200–205PubMedCrossRef
11.
Nedergaard J, Bengtsson T, Cannon B (2011) New powers of brown fat: fighting the metabolic syndrome. Cell Metab 13:238–240PubMedCrossRef
12.
Feldmann HM, Golozoubova V, Cannon B, Nedergaard J (2009) UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab 9:203–209PubMedCrossRef
13.
Golozoubova V, Cannon B, Nedergaard J (2006) UCP1 is essential for adaptive adrenergic nonshivering thermogenesis. Am J Physiol Endocrinol Metab 291:E350–E357PubMedCrossRef
14.
Huttunen P, Hirvonen J, Kinnula V (1981) The occurrence of brown adipose tissue in outdoor workers. Eur J Appl Physiol Occup Physiol 46:339–345PubMedCrossRef
15.
Kang BS, Han DS, Paik KS et al (1970) Calorigenic action of norepinephrine in the Korean women divers. J Appl Physiol 29:6–9PubMed
16.
Hany TF, Gharehpapagh E, Kamel EM, Buck A, Himms-Hagen J, von Schulthess GK (2002) Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur J Nucl Med Mol Imaging 29:1393–1398PubMedCrossRef
17.
Lee P, Zhao JT, Swarbrick MM et al (2011) High prevalence of brown adipose tissue in adult humans. J Clin Endocrinol Metab 96:2450–2455PubMedCrossRef
18.
Vijgen GH, Bouvy ND, Teule GJ, Brans B, Schrauwen P, van Marken Lichtenbelt WD (2011) Brown adipose tissue in morbidly obese subjects. PLoS One 6:e17247PubMedCrossRef
19.
Rothwell NJ, Stock MJ (1979) Regulation of energy balance in two models of reversible obesity in the rat. J Comp Physiol Psychol 93:1024–1034PubMedCrossRef
20.
Astrup A, Bulow J, Madsen J, Christensen NJ (1985) Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. Am J Physiol 248:E507–E515PubMed
21.
Yoneshiro T, Aita S, Kawai Y, Iwanaga T, Saito M (2012) Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. Am J Clin Nutr 95:845–850PubMedCrossRef
22.
Cypess AM, Chen YC, Sze C et al (2012) Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc Natl Acad Sci USA 109:10001–10005PubMedCrossRef
23.
Vosselman MJ, van der Lans AA, Brans B, et al (2012) Systemic beta-adrenergic stimulation of thermogenesis is not accompanied by brown adipose tissue activity in humans. Diabetes (in press)
24.
Dulloo AG, Seydoux J, Girardier L (1991) Peripheral mechanisms of thermogenesis induced by ephedrine and caffeine in brown adipose tissue. Int J Obes 15:317–326PubMed
25.
Ouellet V, Routhier-Labadie A, Bellemare W et al (2011) Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab 96:192–199PubMedCrossRef
26.
Astrup A, Lundsgaard C, Madsen J, Christensen NJ (1985) Enhanced thermogenic responsiveness during chronic ephedrine treatment in man. Am J Clin Nutr 42:83–94PubMed
27.
Yoneshiro T, Aita S, Matsushita M et al (2011) Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring) 19:1755–1760CrossRef
28.
Muzik O, Mangner TJ, Granneman JG (2012) Assessment of oxidative metabolism in brown fat using PET imaging. Front Endocrinol (Lausanne) 3:15
29.
Orava J, Nuutila P, Lidell ME et al (2011) Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab 14:272–279PubMedCrossRef
30.
Ouellet V, Labbe SM, Blondin DP et al (2012) Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 122:545–552PubMedCrossRef
31.
Wu J, Bostrom P, Sparks LM et al (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–376PubMedCrossRef
32.
Torriani M, Fitch K, Stavrou E et al (2012) Deiodinase 2 expression is increased in dorsocervical fat of patients with HIV-associated lipohypertrophy syndrome. J Clin Endocrinol Metab 97:E602–E607PubMedCrossRef
33.
Alkhawaldeh K, Alavi A (2008) Quantitative assessment of FDG uptake in brown fat using standardized uptake value and dual-time-point scanning. Clin Nucl Med 33:663–667PubMedCrossRef
34.
Yoneshiro T, Aita S, Matsushita M et al (2010) Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring) 19:13–16CrossRef
35.
Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J (2010) Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 285:7153–7164PubMedCrossRef
36.
Baba S, Tatsumi M, Ishimori T, Lilien DL, Engles JM, Wahl RL (2007) Effect of nicotine and ephedrine on the accumulation of 18F-FDG in brown adipose tissue. J Nucl Med 48:981–986PubMedCrossRef
37.
Ponrartana S, Aggabao PC, Hu HH, Aldrovandi GM, Wren TA, Gilsanz V (2012) Brown adipose tissue and its relationship to bone structure in pediatric patients. J Clin Endocrinol Metab 97:2693–2698PubMedCrossRef
38.
Lambert GW, Jonsdottir IH (1998) Influence of voluntary exercise on hypothalamic norepinephrine. J Appl Physiol 85:962–966PubMed
39.
Astrup A, Bulow J, Christensen NJ, Madsen J (1984) Ephedrine-induced thermogenesis in man: no role for interscapular brown adipose tissue. Clin Sci (Lond) 66:179–186
40.
Becker DE (1992) Clinical implications of autonomic drugs. J Oral Maxillofac Surg 50:734–740PubMedCrossRef
41.
Jessen K, Rabol A, Winkler K (1980) Total body and splanchnic thermogenesis in curarized man during a short exposure to cold. Acta Anaesthesiol Scand 24:339–344PubMedCrossRef
42.
Joy RJ (1963) Responses of cold-acclimatized men to infused norepinephrine. J Appl Physiol 18:1209–1212PubMed
43.
Napolitano A, Murgatroyd PR, Finer N, et al (2011) Assessment of acute and chronic pharmacological effects on energy expenditure and macronutrient oxidation in humans: responses to ephedrine. J Obes (in press)
44.
Shannon JR, Gottesdiener K, Jordan J et al (1999) Acute effect of ephedrine on 24-h energy balance. Clin Sci (Lond) 96:483–491CrossRef
45.
Sjostrom L, Schutz Y, Gudinchet F, Hegnell L, Pittet PG, Jequier E (1983) Epinephrine sensitivity with respect to metabolic rate and other variables in women. Am J Physiol 245:E431–E442PubMed
46.
van Marken Lichtenbelt WD, Schrauwen P (2011) Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol 301:R285–R296PubMedCrossRef
47.
Davis TR (1961) Chamber cold acclimatization in man. J Appl Physiol 16:1011–1015PubMed
48.
Cannon B, Nedergaard J (2010) Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans). Int J Obes (Lond) 34(Suppl 1):S7–S16CrossRef
49.
Kozak LP, Koza RA (2011) The genetics of brown adipose tissue. Prog Mol Biol Transl Sci 94:75–123CrossRef
50.
Leibel RL, Rosenbaum M, Hirsch J (1995) Changes in energy expenditure resulting from altered body weight. N Engl J Med 332:621–628PubMedCrossRef
Metadaten
Titel
Ephedrine activates brown adipose tissue in lean but not obese humans
verfasst von
A. L. Carey
M. F. Formosa
B. Van Every
D. Bertovic
N. Eikelis
G. W. Lambert
V. Kalff
S. J. Duffy
M. H. Cherk
B. A. Kingwell
Publikationsdatum
01.01.2013
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 1/2013
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2748-1

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